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2016 ; 2016
(ä): 9172157
Nephropedia Template TP
gab.com Text
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English Wikipedia
Oral Administration of N-Acetyl-seryl-aspartyl-lysyl-proline Ameliorates Kidney
Disease in Both Type 1 and Type 2 Diabetic Mice via a Therapeutic Regimen
#MMPMID27088094
Nitta K
; Shi S
; Nagai T
; Kanasaki M
; Kitada M
; Srivastava SP
; Haneda M
; Kanasaki K
; Koya D
Biomed Res Int
2016[]; 2016
(ä): 9172157
PMID27088094
show ga
Kidney fibrosis is the final common pathway of progressive kidney diseases
including diabetic nephropathy. Here, we report that the endogenous antifibrotic
peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), the substrate of
angiotensin-converting enzyme (ACE), is an orally available peptide drug used to
cure kidney fibrosis in diabetic mice. We utilized two mouse models of diabetic
nephropathy, streptozotocin- (STZ-) induced type 1 diabetic CD-1 mice and type 2
diabetic nephropathy model db/db mice. Intervention with the ACE inhibitor
imidapril, oral AcSDKP, or imidapril + oral AcSDKP combination therapy increased
urine AcSDKP levels. AcSDKP levels were significantly higher in the combination
group compared to those of the other groups. AcSDKP oral administration, either
AcSDKP alone or in addition to imidapril, ameliorated glomerulosclerosis and
tubulointerstitial fibrosis. Plasma cystatin C levels were higher in both models,
at euthanasia, and were restored by all the treatment groups. The levels of
antifibrotic miRs, such as miR-29 or let-7, were suppressed in the kidneys of
both models; all treatments, especially the combination of imidapril + oral
AcSDKP, restored the antifibrotic miR levels to a normal value or even higher.
AcSDKP may be an oral antifibrotic peptide drug that would be relevant to
combating fibroproliferative kidney diseases such as diabetic nephropathy.